SIRT4

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View/Edit Human

Sirtuin 4, also known as SIRT4, is a protein which in humans is encoded by the SIRT4 gene.^[1]^[2]

Function

This gene encodes a member of the sirtuin family of proteins which are homologs of the Sir2 gene in budding yeast. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been fully determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA.^[3] Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity.^[1]^[3] The protein encoded by this gene is included in class IV of the sirtuin family.^[2]

SIRT4 is a mitochondrial ADP-ribosyltransferase that inhibits mitochondrial glutamate dehydrogenase 1 activity, thereby downregulating insulin secretion in response to amino acids.^[4] It has been shown that SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells.^[5]

References

↑ ^1.0 ^1.1 Frye RA (June 1999). "Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity". Biochem. Biophys. Res. Commun. 260 (1): 273–9. doi:10.1006/bbrc.1999.0897. PMID 10381378.
↑ ^2.0 ^2.1 "Entrez Gene: Sirtuin 4".
↑ ^3.0 ^3.1 Tanny JC, Dowd GJ, Huang J, Hilz H, Moazed D (December 1999). "An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing". Cell. 99 (7): 735–45. doi:10.1016/S0092-8674(00)81671-2. PMID 10619427.
↑ Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L (September 2006). "SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells". Cell. 126 (5): 941–54. doi:10.1016/j.cell.2006.06.057. PMID 16959573.
↑ Nasrin N, Wu X, Fortier E, Feng Y, Bare' OC, Chen S, Ren X, Wu Z, Streeper RS, Bordone L (October 2010). "SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells. In primary myotubes and hepatocytes, knockdown of SIRT4 results in increased Fatty Acid Oxidation, cellular respiration, and pAMPK levels. SIRT4 inhibition increases fat oxidative capacity in liver and mitochondrial function in muscle, which might provide therapeutic benefits for diseases associated with ectopic lipid storage such as type 2 diabetes". J. Biol. Chem. 285 (42): 31995–2002. doi:10.1074/jbc.M110.124164. PMC 2952200. PMID 20685656.

Yamamoto H, Schoonjans K, Auwerx J (2007). "Sirtuin functions in health and disease". Mol. Endocrinol. 21 (8): 1745–55. doi:10.1210/me.2007-0079. PMID 17456799.
Michishita E, Park JY, Burneskis JM, et al. (2005). "Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins". Mol. Biol. Cell. 16 (10): 4623–35. doi:10.1091/mbc.E05-01-0033. PMC 1237069. PMID 16079181.
Reiling E, van Vliet-Ostaptchouk JV, van 't Riet E, et al. (2009). "Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: the DAMAGE study". Eur. J. Hum. Genet. 17 (8): 1056–62. doi:10.1038/ejhg.2009.4. PMC 2986549. PMID 19209188.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Ahuja N, Schwer B, Carobbio S, et al. (2007). "Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase". J. Biol. Chem. 282 (46): 33583–92. doi:10.1074/jbc.M705488200. PMID 17715127.
"Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. 1998. doi:10.1101/gr.8.11.1097. PMID 9847074.
Frye RA (2000). "Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins". Biochem. Biophys. Res. Commun. 273 (2): 793–8. doi:10.1006/bbrc.2000.3000. PMID 10873683.
Irobi J, Van Impe K, Seeman P, et al. (2004). "Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy". Nat. Genet. 36 (6): 597–601. doi:10.1038/ng1328. PMID 15122253.
Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Scherer SE, Muzny DM, Buhay CJ, et al. (2006). "The finished DNA sequence of human chromosome 12". Nature. 440 (7082): 346–51. doi:10.1038/nature04569. PMID 16541075.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article on a gene on human chromosome 12 is a stub. You can help Wikipedia by expanding it.

[pmid10381378-1] 1.0 ^1.1 Frye RA (June 1999). "Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity". Biochem. Biophys. Res. Commun. 260 (1): 273–9. doi:10.1006/bbrc.1999.0897. PMID 10381378.

[entrez-2] 2.0 ^2.1 "Entrez Gene: Sirtuin 4".

[pmid10619427-3] 3.0 ^3.1 Tanny JC, Dowd GJ, Huang J, Hilz H, Moazed D (December 1999). "An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing". Cell. 99 (7): 735–45. doi:10.1016/S0092-8674(00)81671-2. PMID 10619427.

[pmid16959573-4] Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L (September 2006). "SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells". Cell. 126 (5): 941–54. doi:10.1016/j.cell.2006.06.057. PMID 16959573.

[pmid20685656-5] Nasrin N, Wu X, Fortier E, Feng Y, Bare' OC, Chen S, Ren X, Wu Z, Streeper RS, Bordone L (October 2010). "SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells. In primary myotubes and hepatocytes, knockdown of SIRT4 results in increased Fatty Acid Oxidation, cellular respiration, and pAMPK levels. SIRT4 inhibition increases fat oxidative capacity in liver and mitochondrial function in muscle, which might provide therapeutic benefits for diseases associated with ectopic lipid storage such as type 2 diabetes". J. Biol. Chem. 285 (42): 31995–2002. doi:10.1074/jbc.M110.124164. PMC 2952200. PMID 20685656.

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SIRT4

Function

References

Further reading

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